Dataset Information

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.

ABSTRACT: Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8⁺CD161⁺ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.

SUBMITTER: Peterson LS

PROVIDER: S-EPMC8420969 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.

Peterson Laura S LS Hedou Julien J Ganio Edward A EA Stelzer Ina A IA Feyaerts Dorien D Harbert Eliza E Adusumelli Yamini Y Ando Kazuo K Tsai Eileen S ES Tsai Amy S AS Han Xiaoyuan X Ringle Megan M Houghteling Pearl P Reiss Jonathan D JD Lewis David B DB Winn Virginia D VD Angst Martin S MS Aghaeepour Nima N Stevenson David K DK Gaudilliere Brice B

Frontiers in immunology 20210823

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the ...[more]

PMID: 34497610

Similar Datasets

Project description:Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA), putting them at risk for impaired neurocognitive development. The objective was to determine if a hydrolyzed fat (HF) infant formula containing soy free fatty acids, 2-monoacylglycerolpalmitate, cholesterol, and soy lecithin could increase brain tissue incorporation of essential fatty acids or white matter to enhance brain development in SGA and AGA neonatal piglet models. Sex-matched, littermate pairs of SGA (0.5-0.9kg) and AGA (1.2-1.8kg) 2 day old piglets (N=60) were randomly assigned to control (CON) or HF formula diets in a 2 x 2 factorial design. On day 14, 24 piglets were used for hippocampal RNA-sequencing; the rest began a spatial learning task. On days 26-29, brain structure was assessed by magnetic resonance imaging (MRI). Cerebellum and hippocampus were analyzed for fatty acid content. SGA piglets grew more slowly than AGA piglets, with no effect of diet on daily weight gain or weight at MRI. HF diet did not affect brain weight. HF diet increased relative volumes of 7 brain regions and white matter (WM) volume in both SGA and AGA piglets. However, HF did not ameliorate SGA total WM integrity deficits. RNA sequencing revealed SGA piglets had increased gene expression of synapse and cell signaling pathways and decreased expression of ribosome pathways in the hippocampus compared to AGA. HF decreased expression of immune response related genes in the hippocampus of AGA and SGA piglets, but did not correct gene expression patterns in SGA piglets. Piglets learned the T-maze task at the same rate, but SGA HF, SGA CON, and AGA HF piglets had more accurate performance than AGA CON piglets on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus. HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.

Dataset Information

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.

Publications

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets